AP-HP, Groupe Henri Mondor-Albert Chenevier, Oncology Service, Creteil, France.
Anticancer Res. 2011 Oct;31(10):3507-10.
Therapy of patients with metastatic renal cell carcinoma (mRCC) requires sequential use of several agents with different mechanisms and minimal cross-resistance between the different agents. Tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors prolong progression-free survival (PFS) in patients with mRCC. Re-challenge with TKIs provides clinical benefit after everolimus in patients with mRCC. We report the case of an mRCC patient with lung and bone metastases, treated sequentially with sunitinib, sorafenib and everolimus. The patient had an objective response in reducing bone metastases, but adaptative and concomitant progression in lung metastases during sunitinib re-challenge. Previously, these lung metastases had responded to sunitinib. This intriguing paradox suggests that not only was sunitinib able to target a specific metastatic site during the re-challenge, as seen by the reduction of bone metastases, but it also elicited a more invasive adaptation and progression of lung tumor cells.
转移性肾细胞癌（mRCC）患者的治疗需要序贯使用几种具有不同机制的药物，并且不同药物之间的交叉耐药性最小。酪氨酸激酶抑制剂（TKI）和哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂可延长 mRCC 患者的无进展生存期（PFS）。在 mRCC 患者中使用依维莫司后，再次使用 TKI 可提供临床获益。我们报告了一例 mRCC 患者，该患者患有肺和骨转移，先后接受了舒尼替尼、索拉非尼和依维莫司治疗。在重新接受舒尼替尼治疗时，该患者骨转移得到了客观缓解，但肺转移出现了适应性和伴随性进展。此前，这些肺转移灶对舒尼替尼有反应。这一有趣的悖论表明，舒尼替尼不仅能够在重新挑战时针对特定的转移部位（如骨转移的减少），而且还引发了更具侵袭性的肺肿瘤细胞适应性和进展。
